LIPOPOLYSACCHARIDE INHIBITS ACETYLCHOLINE-MEDIATED AND NITRIC OXIDE-MEDIATED VASODILATION IN-VIVO

The bacterial endotoxin lipopolysaccharide (LPS) inhibits endothelium- dependent relaxation. At present, there is no evidence that this is du e to a diminution in the vasorelaxant potencies of nitric oxide (NO) o r related nitrosyl factors such as S-nitrosocysteine (SNC). The aim of the present study was to determine whether the systemic administratio n of LPS reduces endothelium-dependent vasodilation in rats by diminis hing the vasorelaxant potencies of NO or related nitrosyl factors, We examined the time course of effects of a low dose of LPS (2 mg/kg i.v. ) on base-line mean arterial pressure and vascular resistances and the hemodynamic responses produced by i.v. injection of the endothelium-d ependent vasodilator ACh, the NO donor sodium nitroprusside (SNP) and SNC in urethane-anesthetized rats. LPS produced a sustained fail in me an arterial pressure after 90-120 min due to a reduction in cardiac ou tput, The vasodilator effects of ACh, SNP and SNC in the hindquarter b ed were diminished 30 to 75 min after the administration of LPS. The v asodilator effects of ACh in this bed were unaffected 120 to 180 min a fter LPS. In contrast, the vasodilator effects of SNP were markedly au gmented, whereas those of SNC were markedly diminished, 120 to 180 min after LPS. The vasodilator responses produced by ACR in the renal and mesenteric beds were diminished 30 to 75 min and 120 to 180 min, resp ectively, after LPS. The vasodilator actions of SNP and SNC were not s ubstantially reduced in these beds. These results demonstrate that LPS inhibits ACh-induced vasodilation in vivo. In the hind-quarter bed, t his may involve loss of the vasodilator effectiveness of NO or related nitrosyl factors. In the renal and mesenteric beds, the loss of ACh-i nduced responses may be due to the LPS-induced inhibition of muscarini c receptor-mediated signal transduction mechanisms.